We published this year an investigation of the association of single nucleotide polymorphisms with cerebral palsy in infants born very prematurely, using archived neonatal blood. Four genetic variants were associated with increased risk of cerebral palsy; the targeted genes have roles in inflammation, coagulation, or vasomotor regulation. Using specimens from a population-based study in South Australia and analyses by the Laboratory of Molecular Technology, NCI, we are now examining the association of these and other SNPs with CP across the gestational age spectrum, with the collaboration of Dr. Alastair MacLennan. The association of genotype with preterm and very preterm birth is being explored in this material. Genotyping is also proceeding on DNA from buccal smears from the study of pediatric stroke with Dr. John Lynch. Dr. Lynch has a recent paper on adult stroke, and a paper on pediatric and perinatal stroke, from the NINDS Pediatric Stroke Study, has recently been published. In collaboration with Dr. Robert Yolken we are involved in a study of antibodies to selected bacterial and viral agents in archived neonatal blood of children with cerebral palsy or autism, and control children. With Dr. Phillip Nelson (NICHD) we have examined concentrations of total protein and of certain neurotrophins, neuropeptides, and cytokines in neonatal blood of children with Down syndrome or autism, and examining the developmental trajectory of these substances in the blood of very premature infants, term infants, and healthy adults recruited from the Blood Bank of NIH. Blood concentrations of brain derived neurotrophic factor increased with age, while neurotrophins -3 and -4/5 concentrations were lower in adults than in newborn infants. Values of interleukin-8 were highest in the newborn period, and were higher in infants with Down syndrome than in controls. No differences between infants with later diagnosis of autism vs. controls were observed. A manuscript describing these findings is in press.